The long-term objectives of this proposal include continued efforts to design improved antagonists of the neurohypophysial hormones and to use them as pharmacological probes of the actions of endogenous neurohypophysial hormones. Specific aims include attempts to modify existing antagonists of the antidiuretic action of vasopressin to attain greater potency, specificity and stability. Systematic substitutions and deletions will be made and the resulting analogs will be tested for activities by multiple bioassays. Oxytocin antagonists will also be modified in the hopes of improving potency and specificity. In addition, antagonists and agonists will be iodinated to provide potentially useful radioactive ligands for receptor studies. Agonists and antagonists will be used as pharmacological tools to characterize the brainstem receptors that mediate vasopressin's actions on cardiovascular reflexes. If better oxytocin antagonists are designed they will be used to explore the possible involvement of endogenous oxytocin in initiation of labor. Antagonists of the antidiuretic response promise to become useful therapeutic agents for treating water retention in a variety of circumstances. Oxytocin antagonists could be useful for treating uterine hypermotility and, possibly, premature labor.